Atherosclerosis is a complex process which is generally associated with deposition of fats, cholesterol, fibrin, platelets, cellular debris and calcium, and accompanying formation of plaques, on the luminal wall of vascular endothelial cells. The innermost layer of the artery becomes markedly thickened by these accumulating cells and surrounding material. Sufficient thickening of the arterial wall results in reduction of the diameter of the artery, severely diminishing vascular flow to target organs, leading to morbidity and mortality. The distribution of atherosclerotic plaques is broadly divided into the coronary arteries and the peripheral circulation (most commonly, the lower extremities). Some individuals are primarily affected in the coronary arteries (causing coronary artery disease, “CAD”), in the peripheral arteries (causing peripheral artery disease, “PAD”), while other individuals are substantially affected in both regions. Risk factors for PAD include smoking, hyperlipidemia, hypertension, diabetes, and family history. Untreated PAD can lead to decreased mobility, ulcers, gangrene, and may ultimately require amputation of the affected extremity.
Because of compensatory mechanisms that exist in normal physiologic responses, clinical symptoms of CAD and PAD may not present themselves until the disease has progressed to severe levels. No effective screening tests exist. Both CAD and PAD can be quantified using invasive techniques such as angiography. PAD may be quantitated using a Doppler ultrasound to measure the ankle-brachial index (“ABI”), which entails calculating the ratio of the systolic reading of the pressure in the upper extremity versus the lower extremity. In most healthy individuals, the ratio approaches or is at about 1 (i.e., 0.90 or greater) while in patients with a ratio less than 0.90, PAD is diagnosed. Generally, the lower the ratio, the more severe the disease.
The measurement of the ankle-brachial index is not generally practiced, leading to the under-diagnosis of PAD. Moreover, in patients with diabetes, who constitute greater than 20% of patients with PAD, poor vascular compressibility may cause the ABI test to yield false negatives. Furthermore, ABI does not accurately distinguish PAD patients from long claudicator (“LC”) PAD patients who may have somewhat milder forms of PAD, at least as measured by the decreased pain experienced by LC patients during and after exercise. PAD, when diagnosed early, is amenable to treatments which slow progression of the disease.